2,2'-[[3-chloro-4-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]phenyl]imino]bisethyl bis(hydrogen sulphate), potassium sodium salt

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20-12-2016 to 25-01-2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

30 May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

EPA 712-C-02-190, December 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2'-[[3-chloro-4-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]phenyl]imino]bisethyl bis(hydrogen sulphate), potassium sodium salt

EC Number:

287-719-5

EC Name:

2,2'-[[3-chloro-4-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]phenyl]imino]bisethyl bis(hydrogen sulphate), potassium sodium salt

Cas Number:

85567-07-3

Molecular formula:

C36H42Cl2KN6NaO28S8

IUPAC Name:

2,2'-[[3-chloro-4-[[4-[[2-(sulphooxy)ethyl]sulphonyl]phenyl]azo]phenyl]imino]bisethyl bis(hydrogen sulphate), potassium sodium salt

Test material form:

solid

Details on test material:

Batch: 1283067001

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: step 1: 152 – 165 g; step 2: 155 – 159 g
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet: ad libitum, free access to Altromin 1324 maintenance diet for rats and mice
- Water: e.g. ad libitum, free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: Adequate acclimatisation period (at least five days) under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity:55 ± 10%
- Air changes (per hr): 10 x / hour
- Photoperiod: 12/12 hrs dark / hrs light

IN-LIFE DATES:
From: Acclimatisation Period:
Step 1, animals no. 1 - 3: 29 December 2016 to 04 January 2017
Step 2, animals no. 4 - 6: 05 to 10 January 2017

To: 25 January 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Amount of vehicle (if gavage): The test item was administered at a single dose by gavage using a feeding tube. The test item was administered at a dose volume of 10 mL/kg body weight.
- Justification for choice of vehicle: In order to get the test item in a solution or suspension, which is applicable to the animals, aqua ad injectionem was evaluated as vehicle and was considered to be adequate. This vehicle was chosen due to its non-toxic characteristics.
- Lot/batch no.: AlleMan Pharma, lot no. 605070, expiry date:04/2019

MAXIMUM DOSE VOLUME APPLIED: The test item was administered at a dose volume of 10 mL/kg body weight.

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose was selected to be 2000 mg/kg body weight.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 per step / 2 steps performed

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathological changes. In the absence of gross pathological changes no tissues were preserved for a possible histopathological evaluation.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The rats showed no mortality after a single dose administration.

Clinical signs:

The rats showed no mortality and no other acute oral toxicity characteristics after a single dose administration.

Body weight:

None of the animals showed weight loss during the observation period.

Gross pathology:

No specific gross pathological changes were recorded for any animal.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

A single oral application of the test item to rats at a dose of 2000 mg/kg body weight was not associated with signs of toxicity or mortality. The median lethal dose LD50 cut-off was hence determined to be infinite (∞).

Executive summary:

The oral toxicity of the test substance to rats was assessed according to OECD 423. Two groups, each of three female WISTAR rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was suspended with aqua ad injectionem (sterile water) at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

All animals used in the study were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study without showing any test-item related signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step.

It is therefore concluded that the median lethal dose after a single oral administration to femail rats is LD50 cut-off: infinite (∞)